PurposeThe objective of this study was to evaluate choroidal thickness (CT) in patients with diabetic retinopathy (DR) and normal individuals.Patients and methodsTotally, 60 eyes of patients with diabetes and 25 eyes of normal individuals underwent computed tomography scanning using enhanced-depth imaging spectral-domain optical coherence tomography. Patients with diabetes were classified into four groups: mild, moderate, severe nonproliferative diabetic retinopathy, and proliferative diabetic retinopathy. Manual measurement of CT was carried out at the foveal center and at a distance of 500 µm and 1500 µm in both directions from the fovea. Measurement was taken from the outer limit of the retinal pigment epithelium line to the end of the choroidal image on the optical coherence tomography (choroid–sclera junction).ResultsThe mean subfoveal CT decreased significantly with progression of diabetic retinopathy and diabetic macular edema. However, CT in the control group showed the highest measurements. There was no statistically significant difference in age between the two groups (P>0.05). It was noted that the mean CT was thinnest nasally, followed by thickening subfoveally and thinning again temporally in normal individuals and patients with diabetes.ConclusionCT is altered in diabetes and may be related to the severity of retinopathy. The presence of diabetic macular edema is associated with a significant decrease in CT.

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide [1]. The development of macular edema and proliferative retinopathy are major causes of visual impairment [1],[2].

A healthy choroid is essential for retinal function. Clinical and experimental findings suggested that choroidal vasculopathy in diabetes may play a role in the pathogenesis of DR [3],[4],[5]. Various choroidal abnormalities, including obstruction of the choriocapillaris, vascular degeneration, choroidal aneurysms, and choroidal neovascularization, have been reported in histopathologic studies of diabetic eyes [3],[6],[7].

There are few clinical studies on choroidal angiopathy in diabetes. This is because of the difficulty in imaging the choroid in vivo. Until recently, the choroid could only be evaluated by means of indocyanine green angiography, laser flowmetry, and ultrasonography. However, these techniques are only able to show choroidal vessel abnormalities and blood flow changes. They cannot show the three-dimensional anatomy of choroid layers or the retinal pigment epithelium [8],[9].

Indocyanine green angiography reveals both hyperfluorescent and hypofluorescent spots in diabetic eyes, although the significance is unknown [4],[10]. It has been proposed that the hypofluorescent spots result from ischemic changes in the choroidal vessels and represent either a dye-filling delay or a defect of the choriocapillaris [7],[11]. It is further postulated that the hyperfluorescent spots may be secondary to the presence of choroidal neovascularization, intrachoroidal microvasculature abnormalities, or nodules at the level of the choriocapillaris or underlying stroma [4],[5],[6].

Concurrently, Shiragami et al. [5] described risk factors associated with diabetic choroidopathy, including the presence of severe DR, poor glycemic control, and the nature of the treatment regimen.

In addition, studies assessing the choroidal blood flow beneath the fovea with the use of laser Doppler flowmetry indicate a reduction in choroidal blood flow and volume in patients with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) [12]. There was a more prominent decrease in flow in the case of PDR [13].

A better clinical understanding of choroidal damage might be important for an accurate assessment of diabetic eye disease, but adequate visualization of the choroid using optical coherence tomography (OCT) has not been possible until recently, owing to its posterior location and the presence of pigmented cells that attenuate the incident light [14],[15].

Recent reports showed successful examination and measurement of choroidal thickness (CT) in normal and pathologic states using the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) spectral-domain (SD)-OCT instruments [16],[17],[18]. OCT is a noninvasive imaging modality, which is used in acquiring high-resolution sections of the retina. Recently, enhanced-depth imaging (EDI) SD-OCT has been described. EDI software automatically captures a cross-sectional image with the choroid close to the zero-delay line to maximize sensitivity on the outer limit of the choroid [8],[9].

The present study was designed to determine whether CT is abnormal in patients with various stages of DR and diabetic macular edema (DME).

Patients and methods

This study was conducted as a prospective study on 60 eyes of patients with DR and 25 eyes of normal individuals who were referred to the Ophthalmology Clinic at Minoufia University between June 2014 and December 2015.

The study was approved by the Local Ethical Committee of the Faculty of Medicine, Minoufia University. The nature of the study procedures was explained to all participants before enrollment. All patients signed a written informed consent form.

Eyes were divided into two groups:

Group 1 included 60 eyes having either NPDR or PDR with or without DME.

Group 2 included 25 eyes of normal individuals as a control group.

The study candidate was subjected to full history taking, including age, sex, blood pressure measurement, and past ocular and systemic history. In the diabetic group, further inquiry on diabetes mellitus type, duration, serum hemoglobin A1c level, and previous treatments applied to the eye was carried out. Full ophthalmic examination including visual acuity assessment, intraocular pressure measurement, and anterior segment and posterior segment examination was also performed.

Investigations included fluorescein angiography to determine the stage of DR (in the diabetic group only) and OCT of the macular area and of the choroid using EDI of the Heidelberg Spectralis OCT (in both groups).

Exclusion criteria were as follows:

Uncontrolled systemic arterial blood pressure.

Corneal, lens, or vitreal opacity.

Hyperopia of +3 diopters or more, myopia of −6 diopters or more, high astigmatic error, or irregular astigmatism.

Age-related macular degeneration or choroidal neovascularization.

Having undergone any eye surgery.

Central or branch retinal vein occlusion.

Secondary optic atrophy.

Previous treatment for DR either injection, laser, or surgery.

Choroidal thickness measurement

The subfoveal CT was determined using Spectralis SD-OCT with EDI modality (Heidelberg Engineering, Carlsbad, California, USA). After pupil dilatation using tropicamide 1%, the instrument was placed sufficiently close to the eye to obtain an inverted image to bring the choroidal layer approximate to the zero-delay line.

The images were stacked 100 frames for B-scan using the automatic real-time and eye tracking features, which enabled the capturing of multiple images in the same location. This helped to improve the signal-to-noise ratio and reduce speckle noise. The quality bar indicated that the signal strength of more than 25 was used for acquisition of the image, after which the section going directly through the center of the fovea was selected. The resultant images were viewed and measured with Heidelberg Eye Explorer software (Heidelberg Engineering).

In the macular scans, measurements of CT were performed manually using the calipers provided by the Spectralis Heidelberg software on the center of the fovea and 500 µm and 1500 µm away from the fovea nasally and temporally in horizontal directions and superiorly and inferiorly in vertical directions. The mean vertical and horizontal values were calculated to obtain the mean CT in the center of the fovea and 500 µm and 1500 µm away from the fovea. CT was measured from the outer limit of the retinal pigment epithelium to the choroidal–scleral junction.

The technique of EDI OCT involves placing the objective lens of the SD-OCT device closer to the eye such that an inverted image is obtained. By performing this maneuver, the deeper structures are placed closer to zero delay, allowing better visualization of the choroid. In addition, the thickness of the choroid can be measured at various locations within the macular region.

Results

A total of 85 eyes were included in the study. Of these, 25 eyes were of healthy individuals that served as a control group [six (24%) male and 19 (76%) female], and 60 eyes were of patients with different stages of DR [15 (25%) male and 45 (75%) female]. In the control group, the mean subfoveal CT in male and female was 371 and 336 µm, respectively. In the diabetic group, the mean subfoveal CT in male and female patients was 264 and 238 µm, respectively. There was a significant difference between male and female populations in the two groups (P>0.05).

The mean age of the control group and the mean age of the diabetic patients were 52.88±12.9 and 56.95±8.3 years, respectively. No significant difference in age was observed between the two groups (P>0.05).

The subfoveal CT showed a statistically significant difference between the control group and each group of diabetic patients (P<0.05) ([Table 1]). In addition, there was a statistically significant decrease in CT in patients with DME (P<0.05) ([Table 2]).

The mean subfoveal CT was 354.52±96.51 µm in the control group, 269.4±64.3 µm in the mild NPDR subgroup, 240.7±67 µm in the moderate NPDR subgroup, 227.7±47.9 µm in the severe NPDR subgroup, 220.3±58.1 µm in the PDR subgroup, and 224.4±55.3 µm in the DME group ([Figure 1] and [Figure 2]). An example for CT measurement using EDI SD-OCT is shown in [Figure 3].

A structurally and functionally normal choroidal vasculature is essential for the functioning of the retina. Abnormal choroidal blood volume and/or compromised flow can result in photoreceptor dysfunction and death [6].

The possible role of choroidal vessels in the pathophysiology of DR has been investigated in previous studies. It was found that similar metabolic changes affect the retinal and choroidal vascular beds, and similar growth factors are produced and released in the diabetic choroid and retina. It was suggested that the choroidal vascular system is affected by diabetes and might in fact be involved in the pathogenesis of DR [19].

Recently, the emergence of SD-OCT has allowed the assessment of the choroidal cross-sectional structure and its thickness [14]. EDI can provide a better view of the choroido–scleral interface by bringing the choroid closer to the zero-delay line [20].

In this study, the authors aimed to compare the CT in patients with NPDR, PDR, and DME with that in healthy controls. It was found that the CT decreases as the disease progresses from mild–moderate to severe NPDR to PDR.

Regatieri et al. [21] compared NPDR, PDR, and DME patients with healthy controls using a Cirrus HD-OCT (Carl Zeiss Meditec Inc.) and reported no significant difference between the NPDR and control groups. However, CT was decreased in the PDR and DME groups. In the study by Kim et al. [22], CT was found to be significantly increased as the disease progressed in severity from moderate–severe NPDR to untreated PDR.

In the current study, the CT of patients with DME was significantly thinner than that of non-DME patients. Nagaoka et al. [12] showed that NPDR patients with DME have a reduction in choroidal circulation compared with NPDR patients without DME. They presumed that this decreased circulation could be secondary to retinal hypoxia due to inadequate blood flow, and that this could cause macular edema.

In the present study, CT was thickest in the subfoveal area and became thinner toward the nasal and temporal areas.

SD-OCT is a successful noninvasive device that can be used to evaluate the choroid. Especially in DR, it can be a useful device in evaluating blood flow changes in the choroid. To understand the role of the choroid in DR and its pathophysiology, more prospective studies should be conducted.

Conclusion

CT is altered in diabetes and is related to the severity of retinopathy. The presence of DME is associated with a significant decrease in the CT. SD-OCT is a noninvasive technology to assess the choroid and may be a useful tool in the evaluation of chorioretinal vascular changes in DR.